Heart attack is one of the leading causes of death worldwide, according to Professor Peter Nordstrom of Umea University, Sweden, and colleagues in the European Heart Journal.
They explain that drugs called cholinesterase inhibitors were launched during the 1990s to improve the symptoms of mild to moderate Alzheimer’s disease.
The three such drugs available now are called donepezil (sold as Aricept), rivastigmine (Exelon), and galantamine (Reminyl). They work by reducing the breakdown of the neurotransmitter acetylcholine, through blocking the enzyme acetylcholinesterase.
“These drugs have vagotonic and anti-inﬂammatory properties that could be of interest also with respect to cardiovascular disease,” say the team. In other words, the drugs have a beneficial effect on the heart, including regulating the vagus nerve, which controls the heartbeat.
So the team examined the level of protection by analyzing figures on 7,073 men and women aged about 79 years who had been diagnosed with Alzheimer’s and followed for around 500 days.
Use of these drugs was linked to a significant 34 percent reduction in the risk of heart attack or death from any cause. It also appeared to lower the risk of either outcome individually, by 38 percent for heart attack and 36 percent for death. This benefit remained even when age, sex, type of diagnosis, level of care, and medical history were taken into account.
Patients taking the highest doses had the lowest risk of heart attack or death. However, the findings were not adjusted for statin use, which was unknown.
The authors conclude, “Cholinesterase inhibitor use was associated with a reduced risk of heart attack and death in a nationwide cohort of subjects diagnosed with Alzheimer’s dementia. These associations were stronger with increasing dose.”
Professor Nordstrom commented, “If you translate these reductions in risk into absolute figures, it means that for every 100,000 people with Alzheimer’s disease, there would be 180 fewer heart attacks — 295 as opposed to 475, and 1,125 fewer deaths from all causes, 2,000 versus 3,125 – every year among those taking cholinesterase inhibitors compared to those not using them.”
To see if other dementia drugs have a similar benefit, the team examined data on memantine (sold as Ebixa), used for moderate to advanced Alzheimer’s disease. This drug works differently to cholinesterase inhibitors, and seemed to “make no difference to the risk of heart attack or death from any cause.” But there is some evidence that it is linked to reduced survival among Alzheimer’s patients who do develop cardiovascular disease.
“As far as we know, this is the first time that the use of cholinesterase inhibitors has been linked to a reduced risk of heart attacks and deaths from cardiovascular disease in general or from any cause,” Professor Nordstrom stated.
“As this is an observational study, we cannot say that cholinesterase inhibitor use is causing the reduction in risk, only that it is associated with a reduction. However, the strengths of the associations make them very interesting from the clinical point of view.”
But he cautioned that, although the findings could likely be extended to patients in other countries, “no clinical recommendations should be made on the basis of the results from our study.”
The team now hope that a so-called “meta-analysis” of previous, randomized controlled trials will be carried out, “as this might produce answers on which clinical recommendations could be based.”
A team led by Dr. Toru Kubo of Kochi Medical School, Japan, also did a study that found patients with Alzheimer’s disease who were treated with the cholinesterase inhibitor donepezil had a lower risk of cardiovascular death than did untreated patients.
Looking back on the records of patients taking donepezil suggested that overall risk was of death was lowered by 32 percent and death from cardiovascular causes by 46 percent. Lab tests led the team to believe that this drug benefits the heart through a heart rate lowering effect, via the vagal nerve, as well as a separate protective action directly impacting neurotransmitters in heart cells.
But they caution, “The apparent survival benefit in donepezil-treated patients should not be overinterpreted. Prospective clinical trials are warranted.”
Overall, there seems to be convincing evidence that cholinesterase inhibitor use may cut the risk of heart attack and death in people with Alzheimer’s, but further research to establish this is necessary.
Nordstrom, P. et al. The use of cholinesterase inhibitors and the risk of myocardial infarction and death: a nationwide cohort study in subjects with Alzheimer’s disease. European Heart Journal, doi:10.1093/eurheartj/eht182
Sato, K. et al. The effect of donepezil treatment on cardiovascular mortality. Clinical Pharmacology and Therapeutics, September 2010 doi:10.1038/clpt.2010.98